Expansion of cardiac ischemia/reperfusion injury after instillation of three forms of multi-walled carbon nanotubes

Abstract

BackgroundThe exceptional physical-chemical properties of carbon nanotubes have lead to their use in diverse commercial and biomedical applications. However, their utilization has raised concerns about human exposure that may predispose individuals to adverse health risks. The present study investigated the susceptibility to cardiac ischemic injury following a single exposure to various forms of multi-walled carbon nanotubes (MWCNTs). It was hypothesized that oropharyngeal aspiration of MWCNTs exacerbates myocardial ischemia and reperfusion injury (I/R injury).MethodsOropharyngeal aspiration was performed on male C57BL/6J mice with a single amount of MWCNT (0.01 - 100 μg) suspended in 100 μL of a surfactant saline (SS) solution. Three forms of MWCNTs were used in this study: unmodified, commercial grade (C-grade), and functionalized forms that were modified either by acid treatment (carboxylated, COOH) or nitrogenation (N-doped) and a SS vehicle. The pulmonary inflammation, serum cytokine profile and cardiac ischemic/reperfusion (I/R) injury were assessed at 1, 7 and 28 days post-aspiration.ResultsPulmonary response to MWCNT oropharyngeal aspiration assessed by bronchoalveolar lavage fluid (BALF) revealed modest increases in protein and inflammatory cell recruitment. Lung histology showed modest tissue inflammation as compared to the SS group. Serum levels of eotaxin were significantly elevated in the carboxylated MWCNT aspirated mice 1 day post exposure. Oropharyngeal aspiration of all three forms of MWCNTs resulted in a time and/or dose-dependent exacerbation of myocardial infarction. The severity of myocardial injury varied with the form of MWCNTs used. The N-doped MWCNT produced the greatest expansion of the infarct at any time point and required a log concentration lower to establish a no effect level. The expansion of the I/R injury remained significantly elevated at 28 days following aspiration of the COOH and N-doped forms, but not the C-grade as compared to SS.ConclusionOur results suggest that oropharyngeal aspiration of MWCNT promotes increased susceptibility of cardiac tissue to ischemia/reperfusion injury without a significant pulmonary inflammatory response. The cardiac injury effects were observed at low concentrations of MWCNTs and presence of MWCNTs may pose a significant risk to the cardiovascular system.

Defect density in multiwalled carbon nanotubes influences ovalbumin adsorption and promotes macrophage activation and CD4^+ T-cell proliferation

“…For example, our earlier studies found that MWCNTs with a length of 10-100 μm impaired pulmonary function 22 and induced severe cardiac ischemic/ reperfusion injury after pulmonary instillation. 23 Similar results on MWCNT toxicity were also reported elsewhere, [24][25][26][27] such as subchronic toxicity, asbestos-like pathogenicity in mice, and airway fibrosis. In contrast, CNTs with a length shorter than 2 μm have been shown to exhibit minimal toxicity to various cell types, such as human promyelocytic leukemia (HL60) and human T-cells (Jurkat).…”

One-dimensional nitrogen-containing carbon nanostructures

“…[558]. However, Urankar et al [757] suggested that oropharyngeal aspiration of MWCNT, especially MWNCNTs, produced the greatest expansion of the infarct. The authors suggested that the effect is dependent on the dose and the form of MWCNTs but concluded that, in general, the presence of MWCNTs may pose a significant risk to the cardiovascular system.…”

Subchronic Toxicity and Cardiovascular Responses in Spontaneously Hypertensive Rats after Exposure to Multiwalled Carbon Nanotubes by Intratracheal Instillation

“…11−13 For CNTs, Urankar et al reported that oropharyngeal aspiration of MWCNTs resulted in a time and dose-dependent exacerbation of myocardial infarction when assessed at days 1, 7, and 30 postaspiration. 14 The severity of myocardial injury depended on the form of MWCNTs used. Instillation of SWCNTs in Wistar-Kyoto (WKY) rats was found to alter baroreflex function by affecting cardiovascular autonomic regulation thus contributing to cardiac and arrhythmic events.…”